Catechins are polyphenolic plant metabolites which belong to the flavonoid family. The molecular formula and weight of catechins are C15H14O6 and 290 g/mol. Catechin and epicatechin are epimers, with (−)-epicatechin and (+)-catechin being the most common optical isomers found in nature. Procyanidins or condensed tannins are flavonoid oligomers whose building blocks are (+)-catechin and (−)-epicatechin. They are present abundantly in the plant kingdom in fruits, barks, leaves and seeds where they provide protection against light, oxidation and predators. Procyanidins are found in many plants, mainly apples, pine bark, cinnamon bark, litchi pericarp, peanuts, grape seed, cocoa, grape skin, bilberry, cranberry, black currant, green tea and black tea.
Based on the linkage between the successive monomeric units, procyanidins are classified as Types A, B or C polyphenols. Generally the linkage between successive monomeric units of procyanidins is between the 4th position of the ‘upper’ unit and the 8th position of the ‘lower’ unit, leading to a Type B procyanidin. Alternatively, the linkage can occur between C4 of the ‘upper’ unit and C6 of the lower unit, leading to a Type C procyanidin. Type B and C polyphenols are abundantly seen in many botanical sources. When successive monomeric units are linked by an ether linkage between the C2 and C4 of the ‘upper’ unit and the oxygen at the C7 position and the C6/C8 positions (respectively) of the lower unit, a Type A procyanidin is formed.
Broncho-constrictive conditions are characterized by symptoms of significantly reduced ability to breathe along with coughing and wheezing. This condition produces adverse impact on the airways or bronchioles, which carry air between the bronchi and the alveoli. Inflammation of the bronchioles and clamping of the smooth muscle outside of the bronchioles cause reduced passage of air in or out of the lungs.
Allergic Rhinitis is the most common chronic respiratory illness. It affects quality of life, productivity and is associated with co-morbid conditions such as Asthma. Symptoms of Allergic Rhinitis include rhinorrhea, nasal congestion, obstruction, and pruritus which are triggered by contact with allergens like bacteria, viruses, animal parasites, dust, pollen, chemicals, food, drugs, smoke etc. Asthma is a similar chronic broncho-constrictive condition with airway restriction, mucus production and allergic reaction.
Chronic obstructive pulmonary disease (COPD) is yet another lung disease characterized by chronic bronchitis with symptoms of cough with mucus, wheezing, shortness of breath, fatigue, frequent respiratory infections etc. There is no cure for COPD. Some of the medications used for treatment of COPD are bronchodilators to open the airways, such as ipratropium, tiotropium, salmeterol, or formoterol; and inhaled steroids to reduce lung inflammation.
Bhaskaran et al. (US 2011/0039923 A1) discloses a composition comprising pentameric procyanidin flavonoid of concentration ranging from about 55% w/w to about 99% w/w, trimers and tetramers each at a concentration ranging from about 0.5% w/w to about 35% w/w. This document also discloses a process for preparation of the said composition from plant sources namely Cinnamon, Litchi and Arachis. Further, this document teaches use of the said composition for treatment and management of HIV infection, AIDS and Influenza virus infection. However, this document does not suggest or teach the use of the said composition in treatment, prevention and management of broncho-constrictive conditions.
WO2007053641 A2 teaches that A-type procyanidins inhibit COX-2 gene transcription in a cell line. Based on this cell line experiment it extrapolates and speculates potential anti-inflammatory action in in-vivo conditions. However, this document does not motivate or demonstrate the action of A-type procyanidins in treating, preventing and managing broncho-constrictive conditions namely allergic rhinitis, asthma and COPD. Inhibition of COX-2 enzyme synthesis as discussed by this document has no implication on secretion of leukotrienes. Leukotrienes are the mediators involved in inflammation of the bronchiols or the airway in broncho-constrictive conditions namely allergic rhinitis, asthma and COPD. Moreover, inhibition of COX-2 enzyme can have adverse effect in broncho-constrictive conditions since it inhibits secretion of prostaglandin E2 (PGE2). According to Simmons et al. (2004), PGE2 has bronchoprotective effect in asthma and other pulmonary conditions. For example, aspirin-induced asthma may be triggered by increased release of leukotrienes from inflammatory cells caused by removal of the inhibitory influence of PGE2, a major product of COX-2 in airways. Beside, recent scientific research showed that inhibition of COX-2 has pronounced adverse cardiovascular side effects which lead to withdrawal best selling approved COX-2 inhibitor drugs like Vioxx from the market. Hence, WO2007053641 A2 does not motivate or teach a person skilled in the art to investigate A-type procyanidins for treating, preventing and managing broncho-constrictive conditions namely allergic rhinitis, asthma and COPD.